Acute bronchodilation with an intravenously administered leukotriene D4 antagonist, MK-679.

Abstract

Descriptive studies suggest an association between the release of the cysteinyl leukotrienes and clinical asthma. To help clarify this association, we tested the hypothesis that an intravenous infusion of a potent and specific investigational LTD4 receptor antagonist, MK-679, would cause rapid bronchodilation. In a three-period, randomized, double-blind, crossover study, single doses of MK-679, 125 and 500 mg, and placebo were given intravenously by bolus infusion to nine patients with moderate, stable asthma (FEV1 40 to 80% predicted) on individual study days separated by a week. Spirometry was preformed predose and at intervals for as long as 8 h postdosing; blood samples for MK-679 concentrations were drawn over this time. Fifteen minutes after the end of infusion, the FEV1 percent change from baseline increased a mean of 15.8 +/- 15.7 and 7.8 +/- 11.6% with the 500- and 125-mg doses, respectively, compared with a mean decrease of 2.6 +/- 6.2% with placebo (p = 0.01, overall; p = 0.003, 500 mg versus placebo). The mean end-of-infusion MK-679 plasma concentrations were 86.2 +/- 13.9 and 19.9 +/- 2.7 micrograms/ml for the 500- and 125-mg doses, respectively. MK-679 was well-tolerated, with no significant adverse experiences observed. We conclude that a single, intravenously administered, bolus infusion of MK-679 causes bronchodilation in patients with moderate, stable asthma.

• Authors: N Impens, T F Reiss, J A Teahan, M Desmet, T H Rossing, S Shingo, J Zhang, W Schandevyl, R Verbesselt, A G Dupont
• Journal: The American review of respiratory disease (Am Rev Respir Dis) Vol. 147 Issue 6 Pt 1 Pg. 1442-6 (Jun 1993) ISSN: 0003-0805 [Print] United States
• PMID: 8389106 (Publication Type: Clinical Trial, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)

Chemical References

• Bronchodilator Agents
• Propionates
• Quinolines
• Receptors, Immunologic
• Receptors, Leukotriene
• verlukast

Topics

• Adult
• Analysis of Variance
• Asthma (blood, drug therapy, epidemiology, physiopathology)
• Bronchi (drug effects, physiopathology)
• Bronchodilator Agents (administration & dosage, blood, pharmacology)
• Double-Blind Method
• Female
• Forced Expiratory Volume (drug effects)
• Humans
• Infusions, Intravenous
• Male
• Middle Aged
• Propionates (administration & dosage, blood, pharmacology)
• Quinolines (administration & dosage, blood, pharmacology)
• Receptors, Immunologic (antagonists & inhibitors)
• Receptors, Leukotriene